Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Rel… (NCT06511908) | Clinical Trial Compass
RecruitingPhase 2
Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression
United States50 participantsStarted 2024-11-06
Plain-language summary
Background:
Major depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD.
Objective:
To test a study drug (HNK) in people with MDD.
Eligibility:
People aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254.
Design:
Participants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity.
HNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule:
They will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study.
They will receive no drugs for 2 to 3 weeks.
They will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study.
One set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo.
...
Who can participate
Age range
18 Years – 70 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Ability of participant to understand and willingness to sign a written informed consent document. To verify this, participants must score \>= 80% on the consent quiz.
. Stated willingness to comply with all study procedures and availability for the duration of the study.
. 18 to 70 years of age.
. All participants must have undergone a screening assessment under protocol 01-M-0254.
. Participants must fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Participants must be experiencing a current major depressive episode lasting at least two weeks.
. Participants must have an initial score of \>= 20 on the MADRS and a YMRS score of \<12 within one week of study entry and upon entry into Phase II.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is testing (2R,6R)-HNK, which is a metabolite of ketamine — how does it differ from ketamine itself, and what does that mean for the risks and side effects I might experience?
2Since this is a Phase 2 trial, what do we currently know — and not yet know — about whether (2R,6R)-HNK is safe and effective for treatment-resistant depression, and how does that uncertainty compare to staying on my current treatment plan?
3The trial is measuring changes on the Montgomery-Åsberg Depression Rating Scale — can you help me understand what a meaningful improvement on that scale would actually look like in terms of my day-to-day symptoms?
4Given that my depression hasn't responded to previous treatments, would you recommend I try this trial before or after exploring any remaining standard treatment options that I haven't yet attempted?
5The trial mentions it's relevant to suicide-related outcomes — if I'm experiencing suicidal thoughts, does that make me more or less likely to be considered for this study, and how would my safety be monitored throughout?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Change from baseline on Montgomery-Asberg Depression Rating Scale total scores
. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen.
. Participants must have a current or past history of lack of response to at least one adequate antidepressant trial (may be from the same chemical class), with at least one in the current major depressive episode, operationally defined using the modified Antidepressant Treatment History Form (ATHF); non-response to an adequate trial of ECT or TMS would count as an adequate antidepressant trial.
Exclusion criteria
. Current use of disallowed concomitant medications or transcranial magnetic stimulation (TMS) two weeks prior to the start of Phase II.
. Treatment with a reversible monoamine oxidase inhibitor (MAOI) four weeks prior to the start of Phase II.
. Treatment with fluoxetine, aripiprazole, or brexpiprazole five weeks prior to the start of Phase II.
. Treatment with clozapine or electroconvulsive therapy (ECT) four weeks prior to the start of Phase II.
. Ongoing treatment with moderate or strong CYP3A4/5 inhibitors or inducers
. Lifetime history of deep brain stimulation.
. Previous antidepressant non-response to ketamine or esketamine (full course).
. No structured psychotherapy will be permitted during the total duration of the study. Participants unable or unwilling to stop psychotherapy will be unable to participate in the study.